This proposal is concerned with a broad study of the mechanisms which control inter- and intramolecular interactions in proteins. Particular emphasis will be placed on the thermodynamic and conformational aspects of the solution interactions of proteins with proteins, ligands, and solvent components, and on the interrelations between these. These studies will include: The self-association of brain tubulin to various specific end products in the presence of ionic ligands and the effects of ligands on the self-assembly of microtubules; the differences in the intermolecular contacts in the solution and crystal dimers of chymotrypsin; the mechanisms by which solvent components stabilize proteins in solution, induce crystallization and enhance the self-assembly by organelles; the interactions which stabilize different conformers of an enzyme, alpha- and gamma-chymotrypsins, and their relation to the order of events along the activation path; the circular dichroism spectra of satellite and other unique DNAs, and their relation to conformation and nearest neighbor base frequency. The objective of these studies is to obtain a quantitative understanding on a molecular level of interactions which control the fine structures and self-assemblies of biological macromolecules. It is hoped that such knowledge will lead to a better understanding of how organelles are assembled in living cells and of the manner in which extraneous substances, such as drugs and carcinogenic materials, perform their actions.